In 1919, Abad Santos was instrumental in laying the legal groundwork, as well as drafting the by-laws and constitution of the Philippine Women's University, the country and Asia's first private non-sectarian women's institute of higher learning. A staunch Methodist, Abad Santos worshiped at Central United Methodist Church along T.M. Kalaw Street in Ermita, Manila (then known as the Central Methodist Episcopal Church).

He was later appointed as the first Filipino corporate lawyer of the Philippine National Bank, Manila Railroad Company and other government corporations. He went to the Department of Justice where he became Attorney-General, Undersecretary of Justice then Secretary of Justice from 1921 to 1923. In July 1923, he resigned as Secretary of Justice together with other department secretaries as a result of the controversy between Governor-General Leonard Wood and Filipino leaders.

Abad Santos then served as Chief Counsel of the President of the Senate and the Speaker of the House of Representatives of the Philippines. In 1926, he went to the United States as head of the Philippine Educational Mission. He was again appointed Secretary of Justice in 1928 and re-appointed on July 1, 1931. In 1932, he became an Associate Justice of the Supreme Court. He became its Chief Justice on December 24, 1941. As part of the emergency reorganization of the Commonwealth government, Abad Santos, in his capacity as Chief Justice, was given the responsibilities previously handled by the Secretary of Justice (the position of Secretary of Justice was abolished for the duration of the war). Abad Santos accompanied the Commonwealth government to Corregidor, where on December 30, 1941, he administered the oath of office to President Quezon and Vice-President Osmeña for the second term they'd been elected to in November of that year. He also undertook, with Manuel Roxas, the supervision of the destruction of Commonwealth government currency to prevent its falling into enemy hands.

On April 11, 1942, Abad Santos, his son José Jr. (nicknamed Pepito), Col. Benito Valeriano and two enlisted men were captured by the Japanese in barangayTubod in Barili, Cebu while traveling by automobile to Toledo, Cebu.[1] He identified himself as the Chief Justice of the Supreme Court of the Philippines. He and his son were then taken to a concentration camp in Basak San Nicolas, Cebu City. When asked to cooperate with the Japanese, he refused. Although he had nothing to do with military operations, they imputed to him, as acting president, the destruction of the bridges and other public works in Cebu that had been undertaken by the USAFFE forces to delay the invasion of the island.

The Japanese High Commander Kiyotake Kawaguchi took him and his son aboard a ship on April 26, 1942, thinking they were heading to Manila. Instead, they arrived on April 28 at Parang, Cotabato (now in Maguindanao). The next day they were brought to Malabang, Lanao, arriving on April 30. After two days' confinement at Japanese camps, Chief Justice Abad Santos was called in front of Kawaguchi and was informed about the order of his execution. Before he was shot to death, he was able to talk to his son Pepito. His last parting words to his son were, "Do not cry, Pepito, show to these people that you are brave. It is an honor to die for one's country. Not everybody has that chance." José Abad Santos was executed at 2:00 p.m., on May 7, 1942, under a tall coconut tree near a river bank. He refused to be blindfolded and refused the last cigarette offered to him.[1]

Later that afternoon of May 7, 1942, two Japanese interpreters took José's son, Pepito, to his father's grave. It was a small mound—too small, Pepito thought, to hold his father's remains if properly buried. On top of the grave lay a rock as large as a coconut. Pepito begged that he be allowed to mark the grave with a cross, but his request was denied.

After the war, an intensive search for the place where José was buried failed. Pepito did not find the hut and the trees, which would have served as points of reference for locating the grave. The area where the execution took place had been plowed and planted to root crops.[1]

The date of his execution is often reported as May 7, but as former Supreme Court Justice Ramón C. Aquino, Abad Santos's biographer put it, "This (May 7) was the date given by Pepito himself during his testimony at the trials of Generals Yoshihide Hayashi and Kiyotake Kawaguchi. But on the basis of the testimony of Keiji Fukui, the interpreter during Abad Santos's confinement, supported by notations in his diary, the date of Abad Santos's execution was definitely ascertained to be at two o'clock on the afternoon of May 2, 1942."[2]